Gastroenterology 2017;152:497–514 GUIDELINE Clinical Practice Guidelines for the Use of Video Capsule Robert A. Enns,1 Lawrence Hookey,2 David Armstrong,3 Charles N. Bernstein,4 Steven J. Heitman,5 Christopher Teshima,6 Grigorios I. Leontiadis,3 Frances Tse,3 and Daniel Sadowski7

1Division of Gastroenterology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada; 2Division of Gastroenterology, Department of Medicine, Queen’s University, Kingston, Ontario, Canada; 3Division of Gastroenterology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada; 4Section of Gastroenterology, Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada; 5Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada; 6Division of Gastroenterology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada; 7Division of Gastroenterology, Royal Alexandria Hospital, Edmonton, Alberta, Canada

BACKGROUND & AIMS: Video capsule endoscopy (CE) pro- ideo capsule endoscopy (CE) provides a noninvasive vides a noninvasive option to assess the , but its V method to visualize the small intestine in patients use with respect to endoscopic procedures and cross-sectional with a wide spectrum of disorders such as Crohn’s disease imaging varies widely. The aim of this consensus was to pro- (CD), obscure gastrointestinal (GI) bleeding, polyposis syn- vide guidance on the appropriate use of CE in clinical practice. dromes, celiac disease, and other inflammatory disorders. In METHODS: A systematic literature search identified studies on patients under consideration for CE, initial assessment ’ the use of CE in patients with Crohn s disease, celiac disease, typically includes symptom evaluation, laboratory assess- gastrointestinal bleeding, and anemia. The quality of evidence ment, and endoscopic procedures, as well as cross-sectional and strength of recommendations were rated using the Grading imaging (eg, magnetic resonance enterography [MRE], or of Recommendation Assessment, Development, and Evaluation computed tomography enterography [CTE]) in selected (GRADE) approach. RESULTS: The consensus includes 21 patients. statements focused on the use of small-bowel CE and colon Studies assessing CE generally use radiologic small- capsule endoscopy. CE was recommended for patients with bowel studies or endoscopy as a historical standard for suspected, known, or relapsed Crohn’s disease when ileocolo- noscopy and imaging studies were negative if it was imperative comparison, and assess the incremental diagnostic yield, to know whether active Crohn’s disease was present in the not the diagnostic accuracy, of CE because a gold stan- small bowel. It was not recommended in patients with chronic dard does not exist. There are a number of different abdominal pain or diarrhea, in whom there was no evidence of procedures to assess the small intestine, with substantial abnormal biomarkers typically associated with Crohn’s disease. diversity in investigative approaches evident interna- CE was recommended to assess patients with celiac disease tionally. Some of these issues recently were addressed who have unexplained symptoms despite appropriate treat- through the European Society of Gastrointestinal Endos- ment, but not to make the diagnosis. In patients with overt copy guidelines, which focused on small-bowel investi- gastrointestinal bleeding, and negative findings on esoph- gative devices, including CE, and device-assisted agogastroduodenoscopy and , CE should be enteroscopic techniques.1 The present guideline is performed as soon as possible. CE was recommended only in restricted to CE, and, more specifically, to relevant selected patients with unexplained, mild, chronic iron- questions that are applicable in North America where deficiency anemia. CE was suggested for surveillance in there are somewhat different economic and clinical con- patients with polyposis syndromes or other small-bowel can- cerns. This guideline is focused on the use of CE in adults, cers, who required small-bowel studies. Colon capsule endos- copy should not be substituted routinely for colonoscopy.

Patients should be made aware of the potential risks of CE Abbreviations used in this paper: CAG, Canadian Association of Gastro- including a failed procedure, capsule retention, or a missed enterology; CCE, colon capsule endoscopy; CD, Crohn’s disease; CE, lesion. Finally, standardized criteria for training and reporting capsule endoscopy; CI, confidence interval; CPG, clinical practice fi guideline; CRC, colorectal cancer; CRP, C-reactive protein; CTE, in CE should be de ned. CONCLUSIONS: CE generally should be computed tomography enterography; DBE, double-balloon ; considered a complementary test in patients with gastrointes- EGD, esophagogastroduodenoscopy; FAP, familial adenomatous polypo- tinal bleeding, Crohn’s disease, or celiac disease, who have had sis; FC, fecal calprotectin; GFD, gluten-free diet; GI, gastrointestinal; GRADE, Grading of Recommendation Assessment, Development, and negative or inconclusive endoscopic or imaging studies. Evaluation; IBD, inflammatory bowel disease; IDA, iron-deficiency anemia; MRE, magnetic resonance enterography; PEG, polyethylene glycol; PJS, Peutz–Jeghers Syndrome; RCT, randomized controlled trial. Keywords: Capsule Endoscopy; Video Capsule; Colonoscopy; Most current article Endoscopy; Crohn’s Disease; Celiac Disease; Gastrointestinal © 2017 by the AGA Institute Bleeding. 0016-5085/$36.00 http://dx.doi.org/10.1053/j.gastro.2016.12.032 498 Enns et al Gastroenterology Vol. 152, No. 3 primarily regarding small-bowel CE in patients with Consensus Process known or suspected CD, celiac disease, or gastrointestinal The consensus group included 6 voting participants and a bleeding. nonvoting moderator (D.S.), all of whom were gastroenterolo- gists practicing in Canada with expertise in the use of CE. A web-based consensus platform (ECD Solutions, Atlanta, Materials and Methods GA) administered by the CAG was used to facilitate the Scope and Purpose consensus process in advance of the 1-day face-to-face This consensus was focused on specific questions regarding consensus meeting held in Toronto, Ontario, Canada, in the use of CE as identified and discussed by the participants. November 2015. The meeting co-chairs (R.A.E. and L.H.) Development of this clinical practice guideline was initiated in assisted by Dr Steve Heitman developed the initial statements. November 2014, with a meeting of the full consensus group All participants then reviewed the results of the literature held in November 2015. The entire process took approximately search through the web-based platform, and tagged (selected 20 months, with the final manuscript being submitted for and linked) relevant references to each individual statement. publication in July 2016. Copies of the tagged references were made available to all members of the consensus group. The entire consensus group then voted anonymously on their level of agreement with the Sources and Searches specific statements using a modified Delphi process.8,9 The The Editorial Office of the Cochrane Upper Gastrointestinal statements then were revised to incorporate suggestions from and Pancreatic Diseases Group at McMaster University per- group members. formed a systematic literature search of MEDLINE (1946 on), The consensus conference provided an opportunity for data EMBASE (1980 on), and CENTRAL (Cochrane Central Register to be presented, GRADE evaluations for the statements to be of Controlled Trials) for trials published through January 2014. reviewed, as well as discussion and subsequent finalization of Key search terms included the following: capsule endoscopy, the phrasing for individual statements. Finally, participants video capsule, colonoscop*, esophag*, Pillcam, EndoCapsule, were asked to vote as to their level of agreement for each MiroCam, and CapsoCam. Human studies published in English specific statement. A statement was accepted if more than 75% were considered; additional details of search strategies used in of participants voted a 4 (agree) or 5 (strongly agree) on a scale the preparation of the initial consensus statements are pro- of 1 to 5 (with 1, 2, and 3 being disagree strongly, disagree, and vided online in Appendix 1. Additional focused (but nonsys- uncertain, respectively). tematic) searches also were performed up until October 2015 After acceptance of a statement, participants voted on the before the consensus meeting. strength of the recommendation. A level of agreement of 75% of participants or more was needed to classify a statement as Review and Grading of Evidence strong (we recommend); if this threshold was not met, the statement defaulted to conditional (we suggest). The strength The Grading of Recommendation Assessment, Develop- of the recommendation considered risk-benefit balance, pa- ment, and Evaluation (GRADE) approach2 was used by tients’ values and preferences, cost and resource allocation, and 2 nonvoting methodologists (G.I.L. and F.T.) to assess the the quality of the evidence. Therefore, it is possible for a risk of bias (of individual studies and overall across studies), recommendation to be classified as strong despite having low- indirectness, inconsistency, imprecision, as well as other quality evidence, or conditional despite the existence of high- considerations (including publication bias) to determine the quality evidence.10 As per the GRADE method, a strong overall quality of evidence for each statement. The meth- recommendation is indicative of a more broadly applicable odologists also used Quality Assessment of Diagnostic statement, whereas a conditional recommendation suggests Accuracy Studies-2, a tool using 4 domains (patient selec- that clinicians should “recognize that different choices will be tion, index test, reference standard, and flow and timing) to appropriate for different patients and that they must help each assess the quality of primary diagnostic accuracy studies.3 patient to arrive at a management decision consistent with her The quality of evidence for each statement was graded as or his values and preferences.”10 high, moderate, low, or very low, as described in GRADE2,4 The manuscript initially was drafted by the co-chairs (R.A.E. and prior Canadian Association of Gastroenterology (CAG) and L.H.), after which it was revised based on input from all consensus documents.5,6 GRADE assessments were reviewed members of the consensus group. As per CAG policy for all and agreed upon by voting members of the consensus group clinical practice guidelines, the manuscript was made available at the meeting. to all CAG members for comments before submission for pub- Three statements were determined to meet criteria for lication. Members were notified that the manuscript was “good practice statements”7 in that the consensus group available on the members-only section of the CAG website and believed the recommendation was clinically obvious, and the open for comment for a 2-week period. collection and GRADE analysis of supporting evidence was Written disclosures of any potential conflicts of interest for unnecessary. For these statements (statements 15, 20, and 21), the 24 months before the consensus meeting were provided by although formal GRADE evaluation of the supporting evidence all participants, and made available to all group members, as was not performed, details are provided in the accompanying per CAG policy. sections explaining the group’s rationale. Because approved product labeling varies from country to country, recommendations—based on evidence from the liter- Role of the Funding Sources ature and consensus discussion—may not fully reflect the Funding for the consensus meeting was provided by unre- product labeling for any given country. stricted, arms-length grants to the CAG by Allergan Canada, February 2017 Consensus Guidelines for the Use of CE 499

Covidien Canada ULC, a Medtronic company, and Olympus prospective study, physicians reported that CE helped in Canada Inc. The CAG administered all aspects of the meeting, diagnosing CD in 83% of cases, influenced decision making in and the funding sources had no involvement in the process at 72%, and led to a change in management in 78% of patients.16 any point, and they were not made aware of any part of the In patients who have negative or inconclusive evalu- process from development of search strings and the statements, ations (including ileoscopy, CTE/MRE, or radiography) for to drafting and approval of these guidelines. CD, CE led to an incremental diagnostic yield of 24% in 1 study,17 andshowedgoodsensitivity(93%)andspeci- ficity (84%) in another.18 A trial in 20 pediatric patients Recommendation Statements with suspected CD that was obscure or difficult to di- The individual recommendation statements are pro- agnose by other imaging and endoscopic techniques vided and include the GRADE of supporting evidence and showed multiple lesions that were detected by CE in 50% the voting results, after which, a discussion of the evidence of patients.19 fi considered for the speci c statement is presented. For the Based on the diagnostic yield of CE for the detection of majority of statements the quality of evidence was deter- small-bowel lesions, the consensus group concluded that in mined to be very low, largely because of high risk of bias, patients with inconclusive ileoscopy and imaging and no indirectness, and imprecision. For some statements in which evidence of obstruction, CE is a recommended test. In lower quality of evidence exists, a strong recommendation particular, when there is a failure to visualize the with was made based on other factors such as increased costs of ileoscopy, CE would be preferred to the more invasive unnecessary procedures and lack of appropriate alterna- options of double-balloon endoscopy (DBE) or diagnostic tives, or potential negative consequences of delayed diag- surgery. However, the physician performing and interpret- nosis. A summary of the recommendation statements is ing the CE must be sufficiently experienced to recognize that provided in Table 1. Tables summarizing the most impor- small mucosal breaks or small ulcers are not diagnostic of tant evidence for each of the statements are provided in CD. Because a diagnosis of CD has implications for the Appendix 2. patient’s insurance and disability, as well as the likelihood that medications will be prescribed with potential adverse Crohn’s Disease effects, it is imperative that small-bowel findings interpreted Statement 1. In patients presenting with as CD are definitive, ideally supported by clinical presen- clinical features consistent with Crohn’s disease, and tation and histology. If there is any concern that small-bowel negative ileocolonoscopy and imaging studies, abnormalities identified on CE might represent a diagnosis we recommend capsule endoscopy of the small other than CD then deep enteroscopy should be considered bowel. GRADE: Strong recommendation, very low quality to facilitate tissue acquisition. evidence (Appendix 2 and Supplementary Table 1). Vote: Statement 2. In patients with Crohn’s disease and strongly agree, 83%; agree, 17%. clinical features unexplained by ileocolonoscopy or CD is diagnosed based on clinical symptoms and a imaging studies, we recommend CE. GRADE: Strong combination of endoscopic, histologic, radiologic, and recommendation, very low-quality evidence (Appendix 2 and biochemical investigations.11 A history of diarrhea or Supplementary Table 2). Vote: strongly agree, 100%. abdominal pain for more than 6 weeks,12 and changes in CE also has been shown to have equivalent or higher laboratory investigations such as C-reactive protein (CRP) diagnostic yield than other procedures in patients with level, erythrocyte sedimentation rate, or fecal calprotectin established CD.13 In patients with established CD, a meta- (FC) level,11 as well as the finding of hypoalbuminemia12 or analysis reported significantly greater incremental diag- anemia,11 should suggest the possibility of CD. Typically, nostic yield with small-bowel CE compared with small-bowel ileocolonoscopy, with biopsy, and imaging studies, are rec- barium radiography (small-bowel follow-through or enter- ommended to confirm the diagnosis. oclysis) (38%; 95% CI, 22%–54%; P < .00001) and CTE CE has shown utility for the diagnosis of CD; however, (32%; 95% CI, 16%–47%; P < .0001), but not ileoscopy studies generally assess diagnostic yield, not diagnostic ac- (13%; 95% CI, -1% to 26%; P ¼ .07) or MRE (-6%; 95% CI, curacy, because there is no gold standard (reference stan- -30% to 19%; P ¼ .65).13 CE detected more lesions in the dard) for diagnosis. In addition, few data are available proximal small bowel compared with CTE or MRE.15,20 specifically in patients who had negative alternative studies. A In small studies in patients with known CD, CE provided meta-analysis showed that CE has equivalent, or higher, additional information in 50%–86% of patients, and these diagnostic yield than other procedures in patients with sus- additional findings influenced disease management and pected CD.13 In this meta-analysis of 19 trials there was a clinical outcomes.16,21 significantly greater incremental diagnostic yield with small- Based on findings of improved diagnostic yield, and bowel CE, compared with ileoscopy (22%; 95% confidence evidence that CE can alter patient management, the interval [CI], 5%–39%; P < .00001), radiography (32%; 95% consensus group recommended that studies be performed if CI, 16%–48%; P < .00001), and CTE (47%; 95% CI, 31%– a patient with CD has symptoms that cannot be explained by 63%; P ¼ .009), but not MRE (10%; 95% CI, -14% to 34%; endoscopy or cross-sectional imaging. In this circumstance, P ¼ .43).13 In patients with suspected CD, CE has shown good CE may help to determine whether pathology exists to sensitivity (91%–100%) and specificity (91%–92%) when account for ongoing symptoms that had been missed on using ileocolonoscopy as the reference test.14,15 In a other studies. 500 Enns et al Gastroenterology Vol. 152, No. 3

Table 1.Summary of Consensus Recommendations for the Table 1. Continued Use of Video Capsule Endoscopy Colon capsule ’ Crohn s disease Statement 13. We recommend against the routine substitution Statement 1. In patients presenting with clinical features consistent of colon CE for colonoscopy. GRADE: Strong ’ with Crohn s disease, and negative ileocolonoscopy and recommendation, very low quality evidence. Vote: strongly imaging studies, we recommend capsule endoscopy of the agree, 83%; agree, 17%. small bowel. GRADE: Strong recommendation, very low quality Statement 14. In patients with inflammatory bowel disease (IBD), evidence. Vote: strongly agree, 83%; agree, 17%. we recommend against substituting colon capsule for ’ Statement 2. In patients with Crohn s disease and clinical features colonoscopy to assess the extent and severity of disease. unexplained by ileocolonoscopy or imaging studies, we GRADE: Strong recommendation, very low quality evidence recommend CE. GRADE: Strong recommendation, very low for efficacy, low-quality evidence for safety. Vote: strongly quality evidence. Vote: strongly agree, 100%. agree, 100%. ’ Statement 3. In patients with Crohn s disease, when assessment of Contraindications, cautions, and consent small-bowel mucosal healing (beyond the reach of Statement 15. In patients undergoing CE, we recommend that the ileocolonoscopy) is needed, we suggest CE. GRADE: consent process include disclosure of the potential for a failed Conditional recommendation, very low quality evidence. Vote: procedure, capsule retention, or a missed lesion. GRADE: strongly agree, 33%; agree, 67%. Strong recommendation. Good practice statement, quality of Statement 4. In patients with a suspected small-bowel recurrence evidence not assessed. Vote: strongly agree, 100%. ’ of Crohn s disease after , undiagnosed by Statement 16. In patients with known or suspected strictures of the ileocolonoscopy or imaging studies, we recommend CE. small bowel, we suggest a patency capsule before CE to GRADE: Strong recommendation, very low quality evidence. minimize risk of retention. GRADE: Conditional Vote: strongly agree, 100%. recommendation, very low quality evidence for efficacy, Statement 5. In patients with chronic abdominal pain or diarrhea as low-quality evidence for safety. Vote: strongly agree, 67%; their only symptoms, and no evidence of biomarkers associated agree, 33%. ’ with Crohn s disease, we suggest against the use of CE for the Statement 17. In patients with poor GI motility or chronic narcotic ’ diagnosis of Crohn s disease. GRADE: Conditional use, we recommend confirming that the capsule has reached recommendation, low-quality evidence. Vote: strongly agree, the small bowel within 1 hour of capsule ingestion, and 67%; agree, 33%. continuing the study to the full extent of the battery life of the Celiac disease capsule. GRADE: Strong recommendation, very low quality Statement 6. For patients with suspected celiac disease, we evidence. Vote: strongly agree, 83%; agree, 17%. recommend against CE to make a diagnosis. GRADE: Statement 18. In patients with a pacemaker, we suggest that CE Strong recommendation, very low quality evidence for can be performed without special precautions. GRADE: fi ef cacy, low-quality evidence for safety. Vote: strongly Conditional recommendation, very low quality evidence. Vote: agree, 100%. strongly agree, 50%; agree, 50%. Statement 7. In patients with celiac disease and unexplained Bowel preparation symptoms despite treatment and appropriate investigations, we Statement 19. For patients undergoing CE, we recommend the use recommend CE. GRADE: Strong recommendation, very low of a bowel preparation. GRADE: Strong recommendation, very fi quality evidence for ef cacy, low-quality evidence for safety. low quality evidence for efficacy of prokinetics, low-quality Vote: strongly agree, 83%; agree, 17%. evidence for efficacy of all other bowel preparations. Vote: Gastrointestinal bleeding strongly agree, 100%. Statement 8. In patients who have documented overt GI bleeding Reporting and training fi (excluding hematemesis) and negative ndings on high-quality Statement 20. In patients undergoing CE, we suggest that EGD and colonoscopy, we recommend CE as the next documentation have specific components noted on each diagnostic step. GRADE: Strong recommendation, very low report. GRADE: Conditional recommendation. Good practice quality evidence. Vote: strongly agree, 100%. statement, quality of evidence not assessed. Vote: strongly Statement 9. In patients with an overt, obscure bleeding episode, agree, 67%; agree, 33%. we recommend CE be performed as soon as possible. GRADE: Statement 21. We recommend CE be performed by endoscopists Strong recommendation, very low quality evidence. Vote: with documented competency in the cognitive and technical strongly agree, 83%; agree, 17%. aspects of conducting, reporting, and interpreting CE Statement 10. In patients with prior negative CE who have repeated examinations. GRADE: Strong recommendation. Good practice obscure bleeding, we recommend repeated studies statement, quality of evidence not assessed. Vote: strongly (endoscopy, colonoscopy, and/or CE). GRADE: Strong agree, 83%; agree, 17%. recommendation, very low quality evidence. Vote: strongly agree, 100%. Statement 11. In patients with suspected obscure GI bleeding and unexplained mild chronic iron-deficiency anemia, we recommend CE be used in selected cases. GRADE: Strong Statement 3. In patients with Crohn’s disease, recommendation, low-quality evidence. Vote: strongly agree, when assessment of small-bowel mucosal healing 50%; agree, 50%. (beyond the reach of ileocolonoscopy) is needed, we Polyposis suggest CE. GRADE: Conditional recommendation, very low Statement 12. In patients with polyposis syndromes who require quality evidence (Appendix 2 and Supplementary Table 3). small-bowel studies, we suggest CE for ongoing surveillance. Vote: strongly agree, 33%; agree, 67%. GRADE: Conditional recommendation, very low quality As opposed to the clinical scenario covered in Statement evidence for efficacy, low-quality evidence for safety. Vote: strongly agree, 50%; agree, 50%. 2 of pursuing diagnostic testing in symptomatic patents, this statement addresses the clinical scenario of when a patient has undergone treatment and it is deemed imperative to February 2017 Consensus Guidelines for the Use of CE 501 determine if the active disease identified before treatment require postoperative monitoring where disease has been has resolved. Studies have suggested that symptomatic noted to be isolated to the small bowel (ie, radiologic and response to treatment may not correlate consistently with endoscopic studies are negative), surveillance of the small mucosal healing in patients with CD.22–25 In a prospective intestine with CE is appropriate. case series, despite clinical remission, mucosal healing was Statement 5. In patients with chronic abdominal detected on CE in no patients at week 12, and only in 42% at pain or diarrhea as their only symptoms, and no ’ week 52.23,24 Furthermore, in 1 prospective study of 58 evidence of biomarkers associated with Crohn s patients, changes in CE scores and mucosal healing did not disease, we suggest against the use of CE for the diagnosis of Crohn’s disease. GRADE: Conditional correlate with changes in either CRP level or symptoms recommendation, low-quality evidence (Appendix 2 and associated with treatment.25 However, absolute CE scores Supplementary Table 5). Vote: strongly agree, 67%; agree, have been shown to correlate with symptoms and CRP 33%. levels.25 Because mucosal healing has become a key goal of Studies have shown that the diagnostic yield in patients treatment in patients with CD,26 it is imperative to not rely who only have symptoms is lower than in patients who are solely on self-reported symptoms to determine the extent to positive for biomarkers (eg, CRP, erythrocyte sedimentation which an intervention has been fully successful. A recent rate).31–35 In an analysis of 72 patients with chronic report described the high rate of mucosal disease identified abdominal pain without diarrhea, the diagnostic yield of CE on CE in patients with CD who were in a symptomatic was 66.7% in patients who were positive for inflammatory remission.27 markers compared with 21.4% in those who were nega- Despite the poor correlation between treatment tive.32 In patients with both abdominal pain and diarrhea response and mucosal healing often seen in patients with the impact of inflammatory markers was even more strik- CD, the consensus group suggested that CE was a valid ing, with the diagnostic yield being 90.1% in patients who option in select patients, such as those with multiple were positive compared with 0% in those who were nega- resections or with aggressive proximal or mid–small-bowel tive. The diagnostic yield of CE was 3 times greater in disease that would not be within reach of esophagogas- patients with chronic abdominal pain who were positive for troduodenoscopy (EGD) or ileocolonoscopy, where assess- inflammatory markers compared with those who were ment of extent of ongoing disease activity may be not.35 In a retrospective analysis of patients with symptoms warranted. Patients with multiple resections are at high risk suggestive of CD but negative , FC greater than for retention and appropriate small-bowel imaging (such as 100 mg/g predicted positive CE findings (43%), with FC CTE or MRE) and consideration of patency capsule usually is greater than 200 mg/g providing an even higher diagnostic performed before CE procedures to minimize the risk of yield (65%); in contrast, CE was normal in all patients with retention caused by structural disease. an FC less than 100 mg/g.33 Statement 4. In patients with a suspected ’ The consensus group concluded that CE is not warranted small-bowel recurrence of Crohn s disease after in most patients who present with chronic pain in the colectomy, undiagnosed by ileocolonoscopy or absence of positive tests for inflammatory markers or imaging studies, we recommend CE. GRADE: Strong abnormal findings on endoscopy or imaging. recommendation, very low-quality evidence (Appendix 2 and Supplementary Table 4). Vote: strongly agree, 100%. Studies have suggested that CE can provide additional Celiac Disease information for the diagnosis of postoperative recurrence of Statement 6. For patients with suspected CD in patients who have had ileocolonoscopy with or celiac disease, we recommend against CE to make a – without other imaging studies.28 30 In a prospective study, diagnosis. GRADE: Strong recommendation, very low- CE and ileocolonoscopy were performed within 6 months quality evidence for efficacy, low-quality evidence for safety after surgery in 32 CD patients.29 Among 21 patients with (Appendix 2 and Supplementary Table 6). Vote: strongly recurrence, sensitivity and specificity were 90% and 100% agree, 100%. for ileocolonoscopy, respectively; whereas for CE, sensitivity Celiac disease is diagnosed by endoscopy with was lower at 62%–76%, but specificity was excellent at duodenal biopsies and small-bowel histology showing 90%–100% when compared with ileocolonoscopy. In 2 typical histologic features, with corroborating serologic patients, endoscopic recurrence in the neoterminal ileum evidence and a clinical response to a gluten-free diet was seen by CE but not by ileocolonoscopy. In addition, (GFD).1 Meta-analyses of prospective studies suggest that patients with endoscopic ileal recurrence frequently had CE has good specificity (95%; 95% CI, 89%–98%), how- concurrent jejunal lesions (10 of 21), whereas no proximal ever, sensitivity (89%; 95% CI, 82%–94%) is lower.36,37 lesions were detected in patients with a normal ileum Severe disease was detected more readily on CE than (0 of 10) at CE.29 less severe disease, and most of the studies included The consensus group concluded that CE can provide patients with more severe symptoms and a high pretest additional diagnostic information, and is warranted in probability of celiac disease. This may result in over- patients without strictures or other obstruction who are estimation of the diagnostic accuracy of CE for celiac dis- suspected of having recurrent active disease after surgery ease. In 2 studies, despite positive serology, no patients for CD. Typically, endoscopic or radiologic studies will with negative endoscopy and histology showed mucosal define areas of recurrence in CD. However, for those who changes compatible with celiac disease on CE.38,39 502 Enns et al Gastroenterology Vol. 152, No. 3

The consensus group concluded that even in patients obscure GI bleeding (ie, documented GI blood loss for which with positive serology, CE performed after endoscopy is no cause had been identified) after negative EGD and colo- unlikely to detect any additional patients with celiac disease noscopy.44,45 Diagnostic yield was significantly higher with that had been missed on duodenal biopsy. In addition, if CE CE compared with small-bowel radiography (27% vs 4%; is performed instead of endoscopy and is positive for difference, 23%; 95% CI, 5%–42%)44 and angiography mucosal abnormalities, endoscopic biopsies still would be (53% vs 20%; difference, 33%; 95% CI, 9%–53%; P ¼ required to confirm the diagnosis. Therefore, CE would add .016).45 A subsequent RCT showed a significantly higher little additional information, but could increase the cost of diagnostic yield with CE compared with push-enteroscopy the diagnostic process. (72.5% vs 48.7%; P ¼ .03) in patients with obscure GI Statement 7. In patients with celiac disease and bleeding and negative findings on EGD and colonoscopy.46 unexplained symptoms despite treatment and appro- CE can show additional findings in patients with prior priate investigations, we recommend CE. GRADE: Strong negative endoscopic and imaging studies.47–49 In retro- fi recommendation, very low quality evidence for ef cacy, low- spective and prospective case series, the diagnostic yield of quality evidence for safety (Appendix 2 and Supplementary CE was 50%–72% in patients with obscure overt Table 7). Vote: strongly agree, 83%; agree, 17%. bleeding.48,50–60 One study, in patients with obscure Observational studies in patients with refractory celiac bleeding and prior negative endoscopy with biopsy, found disease have shown that CE has a relatively low incremental that CT enterography was significantly more sensitive than diagnostic yield over endoscopy with histology, but there CE (88% vs 38%; P ¼ .008).61 Similarly, in patients with fi fi may be relevant ndings requiring speci c treatment in overt bleeding without a definitive source seen on CE, CT – 40–43 approximately 15% 30% of patients. CE was shown to enterography was positive in 50% of patients,62 showing – – have a 74% 78% concordance with histology, with a 56% the value of CT enterography, which may be considered – fi 67% sensitivity and an 85% 100% speci city for the complementary in some patients as opposed to mutually 42,43 detection of features of celiac disease. Importantly, CE exclusive. The differences in the results with CE vs CTE at can help identify serious complications of celiac disease, times may have to do with patient selection, which can be including ulcerative jejunoileitis, lymphomas, enteropathy- guided by local referral patterns, as well as ease of avail- fi associated T-cell lymphoma, broepithelial polyps, and ability of these modalities for investigation. In terms of 40,41,43 adenocarcinoma. Comparisons of CE with abdominal longer-term outcomes, some studies have reported a higher cross-sectional imaging in these settings have not been rebleeding rate in patients with positive CE than in those published, likely owing to their uncommon occurrence. with negative CE,53,63 whereas other studies reported no Despite at least 6 months on a GFD, positive serolo- differences in outcomes (although specific treatments may — — gy likely owing to inadvertent gluten use was a frequent be responsible for lowering the rebleeding rates after pos- fi nding in patients with nonresponsive celiac disease itive CE).44,52,55 41,43 (48%). Therefore, before CE it is important to eliminate A meta-analysis found a diagnostic yield of 62% (95% other common etiologies for ongoing symptoms, including CI, 47.3%–76.1%) for CE and 56% (95% CI, 48.9%–62.1%) inadvertent gluten ingestion or lactose intolerance. for DBE, with an odds ratio of 1.39 (95% CI, 0.88–2.20; Lower completion rates for small-bowel CE have been P ¼ .16) for CE in patients with obscure GI bleeding.64 The reported in patients with refractory celiac disease compared diagnostic yield of DBE was significantly higher when per- with a control group without celiac disease (62% vs 87%; formed after a positive CE than after a negative CE. ¼ P .008), however, no cases of capsule retention were In a retrospective cost-effectiveness study, use of CE in 40 reported. patients with obscure bleeding had a higher diagnostic yield The consensus group concluded that CE can be useful in than other imaging procedures, and was associated with a fi patients with refractory celiac disease (de ned as persistent lower cost per positive diagnosis.65 or recurrent symptoms despite 6 months of a GFD), or Based on evidence of a relatively high diagnostic yield patients who respond to treatment but have ongoing or new with CE, the consensus group recommended CE be per- symptoms. Given that endoscopy with biopsy was superior, formed, rather than radiographic studies or angiography, fi and positive serology was a frequent nding in patients with after negative endoscopic studies in hemodynamically sta- 41,43 nonresponsive celiac disease, CE is recommended only if ble patients with overt bleeding. In those patients who are these investigations are negative or fail to explain symptoms. hemodynamically unstable, more urgent endoscopic (deep enteroscopy) or radiologic studies (angiography) may be Gastrointestinal Bleeding more appropriate than CE. In addition, for patients with Statement 8. In patients who have documented hematemesis, indicating an upper GI source of bleeding, overt gastrointestinal (GI) bleeding (excluding hem- repeat endoscopy rather than CE is preferred. atemesis) and negative findings on high-quality EGD Statement 9. In patients with an overt, obscure and colonoscopy, we recommend CE as the next bleeding episode, we recommend CE be performed diagnostic step. GRADE: Strong recommendation, very low as soon as possible. GRADE: Strong recommendation, very quality evidence (Appendix 2 and Supplementary Table 8). low quality evidence (Appendix 2 and Supplementary Vote: strongly agree, 100%. Table 9). Vote: strongly agree, 83%; agree, 17%. Two randomized controlled trials (RCTs) supported the As discussed in statement 8, CE has a diagnostic yield of use of CE over other investigations in patients with overt 50%–72% in patients with overt obscure GI February 2017 Consensus Guidelines for the Use of CE 503

– bleeding.45,48,50 60 In patients who have undergone emer- Statement 11. In patients with suspected obscure gency CE (immediately or within 48 hours), after negative GI bleeding and unexplained mild chronic iron- endoscopy and colonoscopy, CE yielded diagnostic findings deficiency anemia, we recommend CE be used in in 50%–67% of patients.45,66 Evidence suggests that earlier selected cases. GRADE: Strong recommendation, low- CE (within 3 days) was associated with a higher diagnostic quality evidence (Appendix 2 and Supplementary Table 11). yield than after 3 days (44%–72% vs 28%–38%, respec- Vote: strongly agree, 50%; agree, 50%. tively).67,68 In a large retrospective cohort, the diagnostic A meta-analysis of 24 studies (mainly retrospective) yield of CE decreased for each day after admission, from assessed the diagnostic yield of CE in patients with iron- 55% at day 1, 48% at day 2, 29% at day 3, 27% at day 4, deficiency anemia (IDA) who previously had undergone 79 and 18% at day 5.68 In addition, studies have suggested that endoscopy and colonoscopy. The pooled per-patient the diagnostic yield is higher in patients with ongoing overt diagnostic yield was 47% (95% CI, 42%–52%) in 24 bleeding compared with those with prior bleeding.50,69–71 studies including patients with IDA, but also patients Although the European Society of Gastrointestinal undergoing CE for other indications. A subgroup analysis of Endoscopy has recommended that CE be performed within 4 studies (264 patients) that included only patients with 14 days (which is a reasonable goal), the selection of this IDA resulted in a higher diagnostic yield of 66% (95% CI, precise time period could be argued based on the fact that 58%–75%). Subsequent retrospective studies have reported all time periods have not been compared adequately.1 As relatively low rates of positive CE findings in 26%–44% of 80–84 cited earlier, studies have shown only that earlier proced- patients with IDA. In addition, although 1 study sug- ures have higher diagnostic yields, but true long-term out- gested a higher rate of resolution of anemia in patients with 85 comes in terms of patient morbidity and mortality have not positive vs negative CE (100% vs 68%; P ¼ .027), other been studied. Because diagnostic yield appears to decrease studies have not shown an improvement in anemia and with each day of delay, but optimal timing has not been rebleeding rates, irrespective of CE findings or changes in 44,59,86 defined definitively, the consensus group recommended that management. CE be performed as soon as possible in patients with Clinically relevant findings on CE were less likely in ongoing overt bleeding after prior negative studies. patients who had less severe anemia (no prior blood transfusions),80 those with inadequate dietary iron intake, Statement 10. In patients with prior negative CE 82 who have repeated obscure bleeding, we recommend and menorrhagic females. repeated studies (endoscopy, colonoscopy, and/or The consensus group concluded that CE has a moderate CE). GRADE: Strong recommendation, very low quality evi- diagnostic yield in unselected patients with chronic IDA, dence (Appendix 2 and Supplementary Table 10). Vote: although this is unlikely to change management or long- strongly agree, 100%. term outcomes. It is appreciated that determining the In patients with negative CE who have ongoing or exact etiology of iron deficiency (GI bleeding vs other cau- recurrence of obscure bleeding, repeat investigations can ses) may be difficult. However, selected patients with IDA yield positive findings and result in a change in man- can be considered for CE, including males or non- agement.72–75 In RCTs comparing different capsules in menstruating females with more severe anemia (requiring patients who underwent 2 consecutive CE examinations, blood transfusions, hemoglobin level <100 g/L), or those discordant results between the 2 CE procedures were with persistent or recurrent IDA despite adequate iron- reported in approximately 16% of cases.76,77 In a small replacement therapy. cohort study, the diagnostic yield of the single CE was 37.5% for the first CE, 43.8% for the second CE, and 62.5% Polyposis for the combined findings of the back-to-back CEs within a Statement 12. In patients with polyposis syn- 24-hour interval.73 Development of overt bleeding and a dromes, who require small-bowel studies we sug- hemoglobin decrease of 4 g/dL or more have been found to gest CE for ongoing surveillance. GRADE: Conditional be significant predictive factors for a positive second CE.75 recommendation, very low quality evidence for efficacy, low- Patients with on CE, duration of bleeding quality evidence for safety (Appendix 2 and Supplementary for more than 3 months, and ongoing anticoagulant use Table 12). Vote: strongly agree, 50%; agree, 50%. were associated with a higher risk of rebleeding after CE,78 Intestinal polyposis syndromes are relatively rare, and can and may be more likely to benefit from a second procedure. be divided, based on histology, into the broad categories of The consensus group recommended selective repeti- familial adenomatous polyposis (FAP), hamartomatous pol- tion of endoscopy, colonoscopy, or CE based on evidence yposis syndromes, and other rare polyposis syndromes. of positive subsequent yield in some patients with nega- Hamartomatous polyposis syndromes include mainly Peutz– tive CE who experience rebleeding. CT enterography, Jeghers Syndrome (PJS), PTEN-associated hamartomatous balloon enteroscopy, and angiography also may be op- syndromes, familial juvenile polyposis, and Cronkhite–Canada tions in very select cases; local resources and expertise syndrome. Small-bowel polyps occur in more than 75% of FAP mayguidetheuseofthesemodalities.Thechoiceof and PJS patients, with a greater likelihood of jejunal and ileal procedure should be based on patient risk factors, level of polyps in patients who also have duodenal polyps.87,88 Patients suspicion, presenting signs and symptoms, and antici- with hereditary polyposis syndromes are at high risk for pated yield (which is very low in the setting of repeated colorectal cancers, thus surveillance is recommended every negative capsule study). 1–3 years depending on the extent of disease.89 504 Enns et al Gastroenterology Vol. 152, No. 3

Diagnostic test and cohort studies in patients with FAP endoscopic techniques (ie, different endoscopes) or referral or PJS have shown that CE has a better diagnostic yield than to an expert center. endoscopy for the detection of small-bowel polyps, whereas Two studies comparing CCE and CT colonography sug- endoscopy was superior for the detection of duodenal gested that CCE was as good as,102 or better than, CT polyps.87,90,91 CE has been shown to detect more and colonography108 for CRC screening. In patients with smaller jejunal–ileal polyps than other imaging modalities incomplete colonoscopy, CCE detected significant polyps in – including radiography and MRE,88,91 93 and had similar twice as many patients as CT colonography (relative sensi- detection rates to device-assisted enteroscopy94 in patients tivity, 2.0; 95% CI, 1.34–2.98).108 with FAP or PJS. In the meta-analysis, the rate of side effects with CCE Because of the high risk of gastrointestinal com- was 4.1% (95% CI, 2.6%–5.6%), which generally were mild plications, and the demonstrated diagnostic yield of CE, the to moderate (ie, nausea, abdominal pain).96 consensus group recommended CE as part of ongoing sur- A cost-effectiveness study suggested that colonoscopy veillance for patients with polyposis syndromes, especially was more cost effective than CCE if compliance with the 2 those with PJS, who are also at highest risk for bleeding and procedures was the same, however, CCE became more cost intussusception related to small-bowel polyps. effective if compliance with CCE was higher (30%) than with colonoscopy for CRC screening in patients at average Colon Capsule risk.109 Statement 13. We recommend against the routine Based on the higher polyp detection rate with colonos- substitution of colon CE for colonoscopy. GRADE: copy and the added benefit of being able to perform poly- Strong recommendation, very low quality evidence (Appendix pectomy during the same procedure, the consensus group 2 and Supplementary Table 13). Vote: strongly agree, 83%; recommended that CCE not be substituted routinely for agree, 17%. colonoscopy. However, in patients who are unwilling or Meta-analyses95,96 and additional subsequent diagnostic unsuitable for colonoscopy, CCE is an appropriate alterna- – test studies97 101 have suggested that although colon tive. The evidence for the value of CCE is very limited. Even capsule endoscopy (CCE) has a high level of accuracy, it is in the setting of incomplete colonoscopy it is recognized that less sensitive and specific than colonoscopy in patients un- referral to an expert center or alternative methods (ie, DBE) dergoing colorectal cancer (CRC) screening/surveillance or will minimize incomplete rates.110,111 For the small number those with known or suspected colonic diseases. In the of patients who are unwilling to undergo standard colo- meta-analyses, the per-patient sensitivities and specificities noscopy (or it is contraindicated), CCE-2 can be considered. of CCE compared with conventional colonoscopy for detec- The US Food and Drug Administration has approved a CCE tion of any polyp were 71%–73% and 75%–89%, and 68%– for patients after an incomplete optical colonoscopy and, 69% and 82%–86% for the detection of significant polyps more recently, for patients with major risks for colonoscopy (6 mm and/or 3 polyps), respectively.95,96 However, or moderate sedation.112 In addition, Japan’s Pharmaceuti- substantial variability was noted among the included trials cals and Medical Devices Agency has approved a CCE for the in terms of study design, patient populations, and CCE diagnosis of colonic disease when colonoscopy is required technical performance characteristics.95,96 but difficult to conduct, including patients unwilling or All studies in the meta-analyses used first-generation unable to undergo colonoscopy.113 colon capsules (CCE-1); current second-generation colon A drawback of CCE is the preparation, which tradition- capsules (CCE-2) have improved image acquisition ally consisted of a large-volume, polyethylene glycol (PEG)- compared with CCE-1. In studies with CCE-2, reported based initial laxative followed by a booster to accelerate the sensitivities and specificities for detection of any polyp were capsule through the colon. Though the booster was initially 82% and 86%, and for the detection of significant polyps phosphate-based, a more promising magnesium-based (6 mm) were 84%–89% and 64%–88%,97,98,100,102 booster with ascorbic acid, potentially combined with a respectively, a significant improvement compared with motility agent, has been suggested. The extensive laxatives CCE-1. required may hinder patient and physician enthusiasm for In addition to lower sensitivity and specificity than this study. colonoscopy, CCE also is limited by an inability to insufflate Statement 14. In patients with inflammatory the colon, aspirate liquids, control the transit of the CCE, and bowel disease (IBD), we recommend against clean the mucosal surface. Patients with significant polyps substituting colon capsule for colonoscopy to assess on CCE also theoretically will require subsequent poly- the extent and severity of disease. GRADE: Strong pectomy, thereby requiring 2 procedures and increasing recommendation, very low quality evidence for efficacy, low- resource utilization. quality evidence for safety (Appendix 2 and Supplementary In cases in which a previous colonoscopy was incom- Table 14). Vote: strongly agree, 100%. plete103–105 or for patients who are unable/unwilling to CCE has been shown to underestimate the extent and undergo colonoscopy,106,107 CCE has been shown to be a severity of disease compared with colonoscopy in patients reasonable alternative. In this latter group, CCE may have a with ulcerative colitis114,115 or CD.116 In a prospective study positive impact on CRC screening adherence rates.107 On the in patients with known or suspected ulcerative colitis other hand, incomplete are uncommon and (N ¼ 100), the sensitivity and specificity of CCE for the can be completed in most patients through alternative detection of active colonic inflammation were 89% (95% CI, February 2017 Consensus Guidelines for the Use of CE 505

80%–95%) and 75% (95% CI, 51%–90%), respectively.115 retention include known CD,120,125,126,128 strictures or other In patients with active CD of the colon (N ¼ 40), CCE-2 obstruction,126,129 pelvic or abdominal radiation,128,130 or underestimated the severity of disease compared with co- suspected tumor.120,128 Capsule retention may require lonoscopy, and detected colonic ulcerations with 86% endoscopic or surgical retrieval of the capsule.81,126,127 sensitivity and 40% specificity.116 The risk of missed lesions with CE also should be dis- No serious adverse events were reported with cussed with patients. In a retrospective review of 300 CCE-1114,115 or CCE-2,116 but are theoretically possible owing consecutive patients who underwent CE for obscure to the increased diameter of the CCE (eg, capsule retention in bleeding, small-bowel masses were found in 3% of patients, patients with unrecognized small-bowel strictures). duodenal masses were missed in 3 patients (1%) on pre- Based on evidence that CCE is likely to underestimate vious endoscopy, and in 1 patient (0.3%) on CE.127 Cases the extent and severity of IBD, the consensus group have been reported in which, despite a negative CE, malig- concluded that colonoscopy should remain the preferred nant small-bowel pathology was identified by DBE, which procedure to assess active disease in patients with colitis or should be considered when there is a high index of small-bowel disease. suspicion.131 The consensus group unanimously agreed on the impor- Contraindications, Cautions, and Consent tance of informed consent and the need to provide patients fi Statement 15. In patients undergoing CE, we with education regarding the bene ts and risks of CE. recommend that the consent process include disclo- Statement 16. In patients with known or sus- sure of the potential for a failed procedure, capsule pected strictures of the small bowel, we suggest a retention, or a missed lesion. GRADE: Strong recom- patency capsule before CE to minimize risk of mendation. Good practice statement, quality of evidence was retention. GRADE: Conditional recommendation, very low not assessed (Appendix 2 and Supplementary Table 15). Vote: quality evidence for efficacy, low-quality evidence for safety strongly agree, 100%. (Appendix 2 and Supplementary Table 16). Vote: strongly Informed consent is an essential component of good agree, 67%; agree, 33%. clinical practice and ethical physician conduct throughout As discussed in statement 15, the risk of capsule reten- medicine. Therefore, this statement warrants a “good prac- tion in patients with CD can be up to 13%.126 CD, strictures, tice” designation rather than rigorous application of the pelvic or abdominal radiation, and suspected tumors in- GRADE process for assessment of evidence.7 In general, crease the risk of capsule retention. Although strictures studies have shown that effective physician–patient generally are considered a contraindication for CE, not all communication can improve patient quality of life, medical strictures cause enough obstruction to prevent the passage decision making, and clinical outcomes.117–119 The informed of the capsule. consent process is associated with minimal harms or costs, Studies have suggested that passage of an intact patency and the net benefit is large, thus minimizing medical–legal capsule is predictive of successful passage of CE in most risk. patients with known or suspected strictures or a history of – Information provided to patients undergoing CE should obstructive disease.132 136 However, in one retrospective include a discussion of the potential risk, including a failed study including 274 CE procedures, the risk of retention was procedure (capsule fails to exit the or otherwise similar in patients who underwent CE without patency fails to provide definitive visualization of the small bowel); capsule (2.3%) and those who underwent CE after a nega- retention (capsule becomes impacted); or missed small- tive patency capsule (2.1%; P ¼ .9).137 Although CE gener- bowel lesion (ie, false-negative result). In addition, it ally is not administered after a retained patency capsule, in should be emphasized that the small-bowel capsule does not a small number of such patients (n ¼ 18) the retention rate obtain ideal images of the , stomach, and colon. was 11.1%. It is important to note that not all patients in A large case series of CE performed for various in- this study were selected based on history or risk of dications reported incomplete examinations in 20%.120 In a obstruction. systematic review, the pooled completion rate was 84% in Although a patency capsule may identify patients at patients with known or suspected CD.121 Among 20 patients higher risk of retention, data also suggest that imaging with known or suspected CD who underwent both CE and studies,136 or the combination of symptoms and imaging, ileoscopy, incomplete examinations (defined as distal ileal can predict the patency of the small bowel for safe passage evaluations not obtained) occurred in 12% of patients with of the CE.133 In a retrospective study, both patency capsule CE, and in 24% with ileoscopy.122 One patient had both an and imaging studies (such as CT and MRE) had a similar incomplete CE and an incomplete ileoscopy. Fortunately, sensitivity (57% vs 71%; P ¼ 1.00) and specificity (86% vs newer-generation capsules have longer battery life (>12 vs 97%; P ¼ .22) to detect clinically significant small-bowel 8 hours with first-generation capsules), which may increase strictures.136 the duration of the study and completion rates.123,124 The main concern related to use of a patency capsule is Capsule retention has been reported in approximately that patients with false-positive results will be denied CE. – 1.4% of CE procedures.120,121,125 127 Retrospective studies False-positive patency capsule results can occur in patients have reported retention rates of 0% to 1.6% in patients with with delayed transit without obstruction, resulting in suspected IBD, and of 5.2% to 13% in patients with known retention of the patency capsule in the colon rather than IBD.125,126 Patient factors associated with a higher risk of small bowel.136 506 Enns et al Gastroenterology Vol. 152, No. 3

Patency capsules are not without risks. Cases of impac- capsule with a longer battery life to compensate for longer tion requiring surgical removal and delays in dissolution of transit times, use of bowel preparation/simethicone to the patency capsule have been reported,132,133 however, improve visualization, or endoscopic placement of the most reported cases are asymptomatic.135 Abdominal pain capsule into the . was reported in 10% of patients in 1 study.134 Statement 18. In patients with a pacemaker, we Based on evidence of the high predictive value of a suggest that CE can be performed without special negative patency capsule, and the high retention rate in precautions. GRADE: Conditional recommendation, very patients with a positive patency capsule, the consensus low quality evidence (Appendix 2 and Supplementary group recognized the utility of a patency capsule for some Table 18). Vote: strongly agree, 50%; agree, 50%. patients, typically those with obstructive symptomatology Observational data have suggested that CE does not or imaging results suggesting narrowing. However, the interfere with the function of cardiac pacemakers and, retention rate in patients with a positive patency capsule conversely, that pacemakers do not interfere with the ability 143–146 who underwent CE was only 11%, raising concerns about of CE to capture images. An in vitro study found no unnecessarily denying patients a useful test. In addition, interactions between 21 different pacemakers and CE, 145 evidence that imaging studies, or symptoms plus imaging, despite the close proximity of the 2 devices. In a cohort may be as useful as a patency capsule in predicting the study there was no loss of capsule images with pacemaker fi passage of CE, led the consensus group to suggest that this or implantable cardioverter de brillator use, but interfer- strategy may be a reasonable alternative to the use of a ence with image acquisition with left ventricular assist 144 patency capsule in patients with evidence of known or device use was reported. suspected obstruction. The consensus group concluded that, although manu- Therefore, the consensus group suggested that in facturers of CE systems list the presence of a cardiac patients with obstructive symptomatology, imaging should pacemaker or other implanted electromedical devices as a be performed before CE. In patients with negative imaging, contraindication for the use of CE, there appears to be little most investigators will not use a patency capsule. In clinical evidence supporting this. However, less information fi patients with abnormalities, suggesting a high risk of is available for implantable cardioverter de brillators and capsule retention, patency capsules can be considered left ventricular assist devices, and this statement was although some recent data have questioned their benefit.137 limited to the use of pacemakers. Statement 17. In patients with poor GI motility or chronic narcotic use, we recommend confirming that Bowel Preparation the capsule has reached the small bowel within 1 hour Statement 19. For patients undergoing CE, we of capsule ingestion, and continuing the study to the recommend the use of a bowel preparation. GRADE: full extent of the battery life of the capsule. GRADE: Strong recommendation, very low quality evidence for effi- Strong recommendation, very low quality evidence (Appendix cacy of prokinetics, low-quality evidence for efficacy of all 2 and Supplementary Table 17). Vote: strongly agree, 83%; other bowel preparations (Appendix 2 and Supplementary agree, 17%. Table 19). Vote: strongly agree, 100%. Poor GI motility, or delayed transit times related to Systematic reviews and RCTs have shown that adequate chronic narcotic use,138 raise concerns of a higher risk of bowel preparation can improve the quality of visualization failed procedures (eg, poor-quality images or incomplete when used before CE.147–154 A systematic review of 15 RCTs studies) or capsule retention. However, retrospective cohort comparing bowel cleansing with no preparation other than studies have failed to show an increased risk of incomplete a clear fluid diet, found that PEG (1, 2, or 4 L) before CE CE or CE retention related to chronic narcotic use.139,140 significantly increased the odds of adequate visualization Incomplete small-bowel examinations have been reported (odds ratio, 3.13; 95% CI, 1.70–5.75; P ¼ .0002) and diag- in patients with delayed gastric emptying or dysmotility, nostic yield (odds ratio, 1.68; 95% CI, 1.16–2.42; which can lead to slow transit times, but this was not P ¼ .006).147 Sodium phosphate improved the diagnostic associated with an increased risk of retention.140,141 yield (odds ratio, 1.77; 95% CI, 1.18–2.64; P ¼ .005), In a small observational study, despite low CE comple- without affecting visualization quality. PEG plus an anti- tion rates (failure to reach the cecum, or incomplete visu- foaming agent (eg, simethicone) or simethicone alone alization of mucosa), mucosal breaks (ulcerations/erosions) showed significantly improved visualization, but no were seen in 89% of patients with chronic dysmotility.141 improvement in diagnostic yield. Neither bowel preparation Because there does not appear to be an increased risk of nor the use of prokinetics was found to improve completion CE-related adverse events in these patients, and the fact that rates in patients undergoing CE.147 Two RCTs published a significant proportion may have abnormal findings, the after the meta-analysis also reported improved visualization consensus group did not recommend against the use of CE with the combination of PEG þ simethicone, but again no in this population. However, because transit times can be improvements in completion rates.152,153 longer they recommended that steps be taken to ensure Two RCTs comparing low- and high-volume PEG transit to the small bowel. Real-time imaging, with cleansing strategies before CE found no significant differ- interventions if transit is delayed (eg, water or prokinetic), ences in visualization, transit times, cleansing scores, or has been shown to improve completion rates.142 Other steps completion rates between the 2 regimens.153,155 Two that may improve the likelihood of success include using a studies found that administration of low-dose PEG February 2017 Consensus Guidelines for the Use of CE 507

(500 mL), with or without metoclopramide, within 1–2 widely accepted, well-validated rating scale for CE. Most hours of swallowing the capsule also could improve image of the scales have been developed for the assessment of CD, quality.156,157 the most common of which are the Lewis score160–162 and In a systematic review of studies in the setting of colo- the Capsule Endoscopy Crohn’s Disease Activity noscopy, bowel preparations generally were well tolerated Index.163,164 and no clinically significant complications were reported.158 The Capsule Endoscopy Structured Terminology can be In addition to minor electrolyte changes with both prepa- used to report the indications for performing CE and to – rations, PEG tended to cause nausea and bloating, whereas describe the findings.165 167 Although the Smooth, Pro- sodium phosphate was associated with more dizziness and truding lesion Index on Capsule Endoscopy score may have anal irritation.158 clinically useful applications,168 it does not appear to be The consensus group concluded that the benefits of adequately validated and was not recommended. bowel preparation in terms of visualization were sufficient The consensus group suggested that appropriate and to recommend its use before CE, but there was insufficient consistent documentation of CE procedures include the el- evidence to recommend a specific type of preparation. ements shown in Table 2, and encouraged more frequent use of a standardized rating scale, such as the Lewis score for CD, to describe findings on CE. Reporting and Training Statement 21. We recommend CE be performed Statement 20. In patients undergoing CE, we suggest by endoscopists with documented competency in the that documentation have specific components noted cognitive and technical aspects of conducting, on each report. GRADE: Conditional recommendation. Good reporting, and interpreting CE examinations. GRADE: practice statement, quality of evidence was not assessed Strong recommendation. Good practice statement, quality of (Appendix 2 and Supplementary Table 20). Vote: strongly evidence was not assessed (Appendix 2 and Supplementary agree, 67%; agree, 33%. Table 21). Vote: strongly agree, 83%; agree, 17%. Accurate and complete documentation in the medical Credentialing and privileging serve to ensure that pa- record is considered standard clinical practice. Physicians tients receive safe high-quality care from providers with have an ethical, professional, and legal obligation to ensure appropriate skills, training, and experience. The net benefit proper procedural documentation. Therefore, although of the procedure being performed by appropriately trained there is no evidence that procedural documentation with endoscopists possessing documented competence in CE is specific elements can improve patient outcomes, this likely large and unequivocal, and, thus, this statement statement warrants a good practice designation rather than warrants a “good practice” designation.7 rigorous application of the GRADE process for assessment of An important aspect of competency is supervised per- evidence.7 formance of the specific gastroenterology procedure. This The specific elements for documenting CE should mirror has been shown for other procedures such as endoscopic those recommended by the CAG consensus guidelines on retrograde cholangiopancreatography,169,170 and likely is safety and quality indicators in endoscopy (Table 2).159 generalizable to CE. In CE, greater interobserver agreement Standardized reporting allows for the future evaluation of in describing CE findings was seen among more experienced aggregate data for the purpose of process quality improve- endoscopists who perform a greater number of CE ment. Appropriate documentation of the procedure and procedures per year.167 subsequent findings in patients undergoing CE should Specific measures for competency in CE have not yet include standardized elements. been developed. A study to determine minimum training Ideally, relevant findings on CE would be described us- requirements, including a structured CE training program ing an appropriate grading scale. However, there is not a with supervised CE interpretation, determined that trainees

Table 2.Suggested Elements of Capsule Endoscopy Reports

Preprocedure Postprocedure

Capsule system used Quality of bowel preparation Date and time of procedure Extent and completeness of examination Name of reader of capsule output Key times of entry into various portions of GI tract Patient demographics Relevant findings Indication for CE Pertinent negatives Previous investigations Adverse events and resulting interventions Comorbidities Diagnoses Type of bowel preparation Management recommendations Other medication and related information (eg, administration route, antispasmodics, allergies) Information provided to patient and/or family

Adapted from Armstrong et al with permission.159 508 Enns et al Gastroenterology Vol. 152, No. 3 should perform a minimum of 20 supervised procedures studies were negative. However, it was not recommended in to achieve competence in CE.171 Previous endoscopy patients with only chronic abdominal pain or diarrhea, and experience did not impact this finding. The use of a no evidence of biomarkers associated with CD. CE was not computer-based CE training module with video clips and recommended for the diagnosis of celiac disease, but may be multiple-choice questions has been shown to improve lesion useful in patients with unexplained symptoms despite recognition on CE.172 treatment and appropriate investigations. In patients with American Society for Gastrointestinal Endoscopy guide- overt gastrointestinal bleeding and negative findings on lines for credentialing and the granting of privileges to EGD and colonoscopy, CE should be performed as soon as perform CE recommend specific CE training as part of a GI possible. CE may be used in selected patients with chronic fellowship, or an 8-hour interactive continuing medical iron-deficiency anemia. CE is recommended for surveillance education course, followed by performance of 10 CEs that in patients with polyposis syndromes who require small- are reviewed by a credentialed CE endoscopist.173 However, bowel studies. CCE should not be substituted routinely for those guidelines are based on expert opinion. Expert man- colonoscopy, especially in patients with IBD. agement (as opposed to interpretation of the studies) likely requires more experience with specific patient subgroups Canadian Association of undergoing CE. Gastroenterology Statement The consensus group agreed that endoscopists per- This clinical practice guideline (CPG) on the use of video forming procedures should be competent in all aspects of capsule endoscopy was developed under the direction of Drs CE, and should provide an interpretation of the findings Robert A. Enns and Lawrence Hookey, in accordance with the with a consultant opinion, rather than just a technical policies and procedures of the CAG and under the direction report. Documentation of continued competence should be of CAG Clinical Affairs. It has been reviewed by the CAG required for the renewal of CE privileges. However, this Practice Affairs and Clinical Affairs Committees and the CAG cannot be adopted as a requirement until the minimum Board of Directors. The CPG was developed after a thorough number of CE procedures and other objective criteria to consideration of the medical literature and the best available define competency in CE are developed. evidence and clinical experience. It represents the consensus of a Canadian panel comprised of experts on this topic. The Future Directions CPG aims to provide a reasonable and practical approach to care for specialists and allied health professionals charged Although CE has advanced substantially as an important with the duty of providing optimal care to patients and procedure to visualize the small-bowel mucosa, certain families, and can be subject to change as scientific knowledge knowledge gaps have an important impact on the use of CE. and technology advance and as practice patterns evolve. The Standardized criteria should be developed for documenting CPG is not intended to be a substitute for physicians using CE findings, as well as for training and credentialing. More their individual judgment in managing clinical care in information is needed on the extent of bowel preparation consultation with the patient, with appropriate regard to all that should be recommended for CE, and on the role of CE in the individual circumstances of the patient, diagnostic and patients with CD recurrence after surgery, those with pol- treatment options available, and available resources. yposis syndromes, and patients with issues of limited Adherence to these recommendations will not necessarily mobility or narcotics use. produce successful outcomes in every case.

Summary Supplementary Material These guidelines present recommendations for the use of Note: To access the supplementary material accompanying small-bowel CE and CCE in the context of CD, celiac disease, this article, visit the online version of Gastroenterology at and gastrointestinal bleeding. These 21 statements on the use www.gastrojournal.org, and at http://dx.doi.org/10.1053/ of small-bowel CE and CCE also include recommendations j.gastro.2016.12.032. pertaining to training, reporting, and informed consent. The quality of evidence supporting these consensus statements was often very low owing to high risk of bias, References indirectness, and imprecision. However, in many cases 1. Pennazio M, Spada C, Eliakim R, et al. Small-bowel strong recommendations were made based on other factors capsule endoscopy and device-assisted enteroscopy for such as cost and lack of appropriate alternatives. diagnosis and treatment of small-bowel disorders: Eu- These guidelines should help to optimize the use of CE ropean Society of Gastrointestinal Endoscopy (ESGE) and thus help improve patient outcomes. In general, CE is Clinical Guideline. Endoscopy 2015;47:352–376. recommended in patients with negative or inconclusive 2. Guyatt GH, Oxman AD, Vist GE, et al. GRADE: an endoscopic and imaging studies. CE has been shown to emerging consensus on rating quality of evidence and provide additional information and influence disease strength of recommendations. BMJ 2008;336:924–926. management. 3. Whiting PF, Rutjes AW, Westwood ME, et al. QUADAS-2: CE was recommended for patients with suspected, a revised tool for the quality assessment of diagnostic known, or relapsed CD when ileocolonoscopy and imaging accuracy studies. Ann Intern Med 2011;155:529–536. February 2017 Consensus Guidelines for the Use of CE 509

4. Sultan S, Falck-Ytter Y, Inadomi JM. The AGA institute 20.Voderholzer WA, Beinhoelzl J, Rogalla P, et al. process for developing clinical practice guidelines part Small bowel involvement in Crohn’s disease: a pro- one: grading the evidence. Clin Gastroenterol Hepatol spective comparison of wireless capsule endoscopy 2013;11:329–332. and computed tomography enteroclysis. Gut 2005; 5. Bressler B, Marshall JK, Bernstein CN, et al. Clinical 54:369–373. practice guidelines for the medical management of 21.Lorenzo-Zuniga V, de Vega VM, Domenech E, et al. nonhospitalized ulcerative colitis: the Toronto Impact of capsule endoscopy findings in the manage- consensus. Gastroenterology 2015;148:1035–1058 e3. ment of Crohn’s disease. Dig Dis Sci 2010;55:411–414. 6. Nguyen GC, Bernstein CN, Bitton A, et al. Consensus 22.Efthymiou A, Viazis N, Mantzaris G, et al. Does clinical statements on the risk, prevention, and treatment of response correlate with mucosal healing in patients with venous thromboembolism in inflammatory bowel dis- Crohn’s disease of the small bowel? A prospective, ease: Canadian Association of Gastroenterology. case-series study using wireless capsule endoscopy. Gastroenterology 2014;146:835–848 e6. Inflamm Bowel Dis 2008;14:1542–1547. 7. Guyatt GH, Schunemann HJ, Djulbegovic B, et al. 23.Hall B, Holleran G, Chin JL, et al. A prospective 52 week Guideline panels should not GRADE good practice mucosal healing assessment of small bowel Crohn’s statements. J Clin Epidemiol 2015;68:597–600. disease as detected by capsule endoscopy. J Crohns 8. Dalkey N. An experimental study of group opinion: the Colitis 2014;8:1601–1609. Delphi method. Futures 1969;1:408–426. 24.Hall BJ, Holleran GE, Smith SM, et al. A prospective 12- 9. Cook DJ, Greengold NL, Ellrodt AG, et al. The relation week mucosal healing assessment of small bowel between systematic reviews and practice guidelines. Ann Crohn’s disease as detected by capsule endoscopy. Eur Intern Med 1997;127:210–216. J Gastroenterol Hepatol 2014;26:1253–1259. 10.Guyatt GH, Oxman AD, Kunz R, et al. Going from evi- 25.Yang L, Ge ZZ, Gao YJ, et al. Assessment of capsule dence to recommendations. BMJ 2008;336:1049–1051. endoscopy scoring index, clinical disease activity, and 11.Van Assche G, Dignass A, Panes J, et al. The second C-reactive protein in small bowel Crohn’s disease. European evidence-based consensus on the diagnosis J Gastroenterol Hepatol 2013;28:829–833. and management of Crohn’s disease: definitions and 26.Lichtenstein GR, Hanauer SB, Sandborn WJ, et al. diagnosis. J Crohns Colitis 2010;4:7–27. Management of Crohn’s disease in adults. Am J 12.Sands BE. From symptom to diagnosis: clinical distinc- Gastroenterol 2009;104:465–483; quiz 464, 484. tions among various forms of intestinal inflammation. 27.Kopylov U, Yablecovitch D, Lahat A, et al. Detection of Gastroenterology 2004;126:1518–1532. small bowel mucosal healing and deep remission in pa- 13.Dionisio PM, Gurudu SR, Leighton JA, et al. Capsule tients with known small bowel Crohn’s disease using endoscopy has a significantly higher diagnostic yield in biomarkers, capsule endoscopy, and imaging. Am J patients with suspected and established small-bowel Gastroenterol 2015;110:1316–1323. Crohn’s disease: a meta-analysis. Am J Gastroenterol 28.Albert JG, Martiny F, Krummenerl A, et al. Diagnosis of 2010;105:1240–1248; quiz 1249. small bowel Crohn’s disease: a prospective comparison 14.Casciani E, Masselli G, Di Nardo G, et al. MR enter- of capsule endoscopy with magnetic resonance imaging ography versus capsule endoscopy in paediatric patients and fluoroscopic enteroclysis. Gut 2005;54:1721–1727. with suspected Crohn’s disease. Eur Radiol 2011; 29.Bourreille A, Jarry M, D’Halluin PN, et al. Wireless 21:823–831. capsule endoscopy versus ileocolonoscopy for the 15.Jensen MD, Nathan T, Rafaelsen SR, et al. Diagnostic diagnosis of postoperative recurrence of Crohn’s accuracy of capsule endoscopy for small bowel Crohn’s disease: a prospective study. Gut 2006;55:978–983. disease is superior to that of MR enterography or 30.Biancone L, Calabrese E, Petruzziello C, et al. Wireless CT enterography. Clin Gastroenterol Hepatol 2011; capsule endoscopy and small intestine contrast ultra- 9:124–129. sonography in recurrence of Crohn’s disease. Inflamm 16.Gralnek IM, Cohen SA, Ephrath H, et al. Small bowel Bowel Dis 2007;13:1256–1265. capsule endoscopy impacts diagnosis and management 31.Bardan E, Nadler M, Chowers Y, et al. Capsule of pediatric inflammatory bowel disease: a prospective endoscopy for the evaluation of patients with chronic study. Dig Dis Sci 2012;57:465–471. abdominal pain. Endoscopy 2003;35:688–689. 17.Adler SN, Yoav M, Eitan S, et al. Does capsule endos- 32.Katsinelos P, Fasoulas K, Beltsis A, et al. Diagnostic yield copy have an added value in patients with perianal dis- and clinical impact of wireless capsule endoscopy in ease and a negative work up for Crohn’s disease? World patients with chronic abdominal pain with or without J Gastrointest Endosc 2012;4:185–188. diarrhea: a Greek multicenter study. Eur J Intern Med 18.Girelli CM, Porta P, Malacrida V, et al. Clinical outcome 2011;22:e63–e66. of patients examined by capsule endoscopy for sus- 33.Koulaouzidis A, Douglas S, Rogers MA, et al. Fecal cal- pected small bowel Crohn’s disease. Dig Liver Dis 2007; protectin: a selection tool for small bowel capsule 39:148–154. endoscopy in suspected IBD with prior negative bi- 19.Guilhon de Araujo Sant’Anna AM, Dubois J, Miron MC, directional endoscopy. Scand J Gastroenterol 2011; et al. Wireless capsule endoscopy for obscure small-bowel 46:561–566. disorders: final results of the first pediatric controlled trial. 34.Koulaouzidis A, Douglas S, Plevris JN. Lewis score cor- Clin Gastroenterol Hepatol 2005;3:264–270. relates more closely with fecal calprotectin than Capsule 510 Enns et al Gastroenterology Vol. 152, No. 3

Endoscopy Crohn’s Disease Activity Index. Dig Dis Sci 50.Carey EJ, Leighton JA, Heigh RI, et al. A single-center 2012;57:987–993. experience of 260 consecutive patients undergoing 35.May A, Manner H, Schneider M, et al. Prospective capsule endoscopy for obscure gastrointestinal multicenter trial of capsule endoscopy in patients with bleeding. Am J Gastroenterol 2007;102:89–95. chronic abdominal pain, diarrhea and other signs and 51.Chami G, Raza M, Bernstein CN. Usefulness and impact symptoms (CEDAP-Plus Study). Endoscopy 2007; on management of positive and negative capsule 39:606–612. endoscopy. Can J Gastroenterol 2007;21:577–581. 36.El-Matary W, Huynh H, Vandermeer B. Diagnostic char- 52.Hindryckx P, Botelberge T, De Vos M, et al. Clinical acteristics of given video capsule endoscopy in diag- impact of capsule endoscopy on further strategy and nosis of celiac disease: a meta-analysis. J Laparoendosc long-term clinical outcome in patients with obscure Adv Surg Tech A 2009;19:815–820. bleeding. Gastrointest Endosc 2008;68:98–104. 37.Rokkas T, Niv Y. The role of video capsule endoscopy in 53.Lai LH, Wong GL, Chow DK, et al. Long-term follow-up the diagnosis of celiac disease: a meta-analysis. Eur J of patients with obscure gastrointestinal bleeding after Gastroenterol Hepatol 2012;24:303–308. negative capsule endoscopy. Am J Gastroenterol 2006; 38.Lidums I, Cummins AG, Teo E. The role of capsule 101:1224–1228. endoscopy in suspected celiac disease patients with 54.Matsumura T, Arai M, Sazuka S, et al. Negative capsule positive celiac serology. Dig Dis Sci 2011;56:499–505. endoscopy for obscure gastrointestinal bleeding is 39.Rondonotti E, Spada C, Cave D, et al. Video capsule closely associated with the use of low-dose aspirin. enteroscopy in the diagnosis of celiac disease: a multi- Scand J Gastroenterol 2011;46:621–626. center study. Am J Gastroenterol 2007;102:1624–1631. 55.Park JJ, Cheon JH, Kim HM, et al. Negative capsule 40.Barret M, Malamut G, Rahmi G, et al. Diagnostic yield of endoscopy without subsequent enteroscopy does capsule endoscopy in refractory celiac disease. Am J not predict lower long-term rebleeding rates in patients Gastroenterol 2012;107:1546–1553. with obscure GI bleeding. Gastrointest Endosc 2010; 41.Kurien M, Evans KE, Aziz I, et al. Capsule endoscopy in 71:990–997. adult celiac disease: a potential role in equivocal cases of 56.Redondo-Cerezo E, Perez-Vigara G, Perez-Sola A, et al. celiac disease? Gastrointest Endosc 2013;77:227–232. Diagnostic yield and impact of capsule endoscopy on 42.Maiden L, Elliott T, McLaughlin SD, et al. A blinded pilot management of patients with gastrointestinal bleeding of comparison of capsule endoscopy and small bowel obscure origin. Dig Dis Sci 2007;52:1376–1381. histology in unresponsive celiac disease. Dig Dis Sci 57.Sakai E, Endo H, Taniguchi L, et al. Factors predicting 2009;54:1280–1283. the presence of small bowel lesions in patients with 43.Atlas DS, Rubio-Tapia A, Van Dyke CT, et al. Capsule obscure gastrointestinal bleeding. Dig Endosc 2013; endoscopy in nonresponsive celiac disease. Gastrointest 25:412–420. Endosc 2011;74:1315–1322. 58.Saperas E, Dot J, Videla S, et al. Capsule endoscopy 44.Laine L, Sahota A, Shah A. Does capsule endoscopy versus computed tomographic or standard angiography improve outcomes in obscure gastrointestinal bleeding? for the diagnosis of obscure gastrointestinal bleeding. Randomized trial versus dedicated small bowel radiog- Am J Gastroenterol 2007;102:731–737. raphy. Gastroenterology 2010;138:1673–1680 e1; quiz 59.Sheibani S, Levesque BG, Friedland S, et al. Long-term e11–e12. impact of capsule endoscopy in patients referred for 45.Leung WK, Ho SS, Suen BY, et al. Capsule endoscopy or iron-deficiency anemia. Dig Dis Sci 2010;55:703–708. angiography in patients with acute overt obscure 60.Toy E, Rojany M, Sheikh R, et al. Capsule endoscopy’s gastrointestinal bleeding: a prospective randomized impact on clinical management and outcomes: a single- study with long-term follow-up. Am J Gastroenterol center experience with 145 patients. Am J Gastroenterol 2012;107:1370–1376. 2008;103:3022–3028. 46.Segarajasingam DS, Hanley SC, Barkun AN, et al. Ran- 61.Huprich JE, Fletcher JG, Fidler JL, et al. Prospective domized controlled trial comparing outcomes of video blinded comparison of wireless capsule endoscopy and capsule endoscopy with push enteroscopy in obscure multiphase CT enterography in obscure gastrointestinal gastrointestinal bleeding. Can J Gastroenterol Hepatol bleeding. Radiology 2011;260:744–751. 2015;29:85–90. 62.Agrawal JR, Travis AC, Mortele KJ, et al. Diagnostic yield 47.Hartmann D, Schmidt H, Bolz G, et al. A prospective two- of dual-phase computed tomography enterography in center study comparing wireless capsule endoscopy patients with obscure gastrointestinal bleeding and a with intraoperative enteroscopy in patients with obscure non-diagnostic capsule endoscopy. J Gastroenterol GI bleeding. Gastrointest Endosc 2005;61:826–832. Hepatol 2012;27:751–759. 48.Heo HM, Park CH, Lim JS, et al. The role of capsule 63.Riccioni ME, Urgesi R, Cianci R, et al. Negative capsule endoscopy after negative CT enterography in patients endoscopy in patients with obscure gastrointestinal with obscure gastrointestinal bleeding. Eur Radiol 2012; bleeding reliable: recurrence of bleeding on long-term 22:1159–1166. follow-up. World J Gastroenterol 2013;19:4520–4525. 49.Tacheci I, Deviere J, Kopacova M, et al. The importance 64.Teshima CW, Kuipers EJ, van Zanten SV, et al. Double of upper gastrointestinal lesions detected with capsule balloon enteroscopy and capsule endoscopy for obscure endoscopy in patients with obscure digestive bleeding. gastrointestinal bleeding: an updated meta-analysis. Acta Gastroenterol Belg 2011;74:395–399. J Gastroenterol Hepatol 2011;26:796–801. February 2017 Consensus Guidelines for the Use of CE 511

65.Marmo R, Rotondano G, Rondonotti E, et al. Capsule 80.Koulaouzidis A, Yung DE, Lam JH, et al. The use of enteroscopy vs. other diagnostic procedures in diag- small-bowel capsule endoscopy in iron-deficiency ane- nosing obscure gastrointestinal bleeding: a cost- mia alone; be aware of the young anemic patient. Scand effectiveness study. Eur J Gastroenterol Hepatol 2007; J Gastroenterol 2012;47:1094–1100. 19:535–542. 81.Rondonotti E, Soncini M, Girelli C, et al. Small bowel 66.Lecleire S, Iwanicki-Caron I, Di-Fiore A, et al. Yield and capsule endoscopy in clinical practice: a multicenter impact of emergency capsule enteroscopy in severe 7-year survey. Eur J Gastroenterol Hepatol 2010; obscure-overt gastrointestinal bleeding. Endoscopy 22:1380–1386. 2012;44:337–342. 82.Tong J, Svarta S, Ou G, et al. Diagnostic yield of capsule 67.Esaki M, Matsumoto T, Yada S, et al. Factors associated endoscopy in the setting of iron deficiency anemia with the clinical impact of capsule endoscopy in patients without evidence of gastrointestinal bleeding. Can J with overt obscure gastrointestinal bleeding. Dig Dis Sci Gastroenterol 2012;26:687–690. 2010;55:2294–2301. 83.van Turenhout ST, Jacobs MA, van Weyenberg SJ, et al. 68.Singh A, Marshall C, Chaudhuri B, et al. Timing of video Diagnostic yield of capsule endoscopy in a tertiary hos- capsule endoscopy relative to overt obscure GI bleeding: pital in patients with obscure gastrointestinal bleeding. implications from a retrospective study. Gastrointest J Gastrointest Liver Dis 2010;19:141–145. Endosc 2013;77:761–766. 84.Sidhu R, McAlindon ME, Kapur K, et al. Push entero- 69.Ge ZZ, Chen HY, Gao YJ, et al. Best candidates for scopy in the era of capsule endoscopy. J Clin capsule endoscopy for obscure gastrointestinal Gastroenterol 2008;42:54–58. bleeding. J Gastroenterol Hepatol 2007;22:2076–2080. 85.Apostolopoulos P, Liatsos C, Gralnek IM, et al. The role 70.Pennazio M, Santucci R, Rondonotti E, et al. Outcome of of wireless capsule endoscopy in investigating unex- patients with obscure gastrointestinal bleeding after plained iron deficiency anemia after negative endoscopic capsule endoscopy: report of 100 consecutive cases. evaluation of the upper and lower . Gastroenterology 2004;126:643–653. Endoscopy 2006;38:1127–1132. 71.Yamada A, Watabe H, Kobayashi Y, et al. Timing of 86.Holleran GE, Barry SA, Thornton OJ, et al. The use of capsule endoscopy influences the diagnosis and small bowel capsule endoscopy in iron deficiency outcome in obscure-overt gastrointestinal bleeding. anaemia: low impact on outcome in the medium term Hepatogastroenterology 2012;59:676–679. despite high diagnostic yield. Eur J Gastroenterol 72.Lorenceau-Savale C, Ben-Soussan E, Ramirez S, et al. Hepatol 2013;25:327–332. Outcome of patients with obscure gastrointestinal 87.Schulmann K, Hollerbach S, Kraus K, et al. Feasibility bleeding after negative capsule endoscopy: results of a and diagnostic utility of video capsule endoscopy for the one-year follow-up study. Gastroenterol Clin Biol 2010; detection of small bowel polyps in patients with heredi- 34:606–611. tary polyposis syndromes. Am J Gastroenterol 2005; 73.Min BH, Chang DK, Kim BJ, et al. Does back-to-back 100:27–37. capsule endoscopy increase the diagnostic yield over a 88.Burke CA, Santisi J, Church J, et al. The utility of capsule single examination in patients with obscure gastrointes- endoscopy small bowel surveillance in patients with tinal bleeding? Gut Liver 2010;4:54–59. polyposis. Am J Gastroenterol 2005;100:1498–1502. 74.Svarta S, Segal B, Law J, et al. Diagnostic yield of 89.Cairns SR, Scholefield JH, Steele RJ, et al. Guidelines for repeat capsule endoscopy and the effect on subse- colorectal cancer screening and surveillance in moderate quent patient management. Can J Gastroenterol 2010; and high risk groups (update from 2002). Gut 2010; 24:441–444. 59:666–689. 75.Viazis N, Papaxoinis K, Vlachogiannakos J, et al. Is there 90.Iaquinto G, Fornasarig M, Quaia M, et al. Capsule a role for second-look capsule endoscopy in patients endoscopy is useful and safe for small-bowel surveil- with obscure GI bleeding after a nondiagnostic first test? lance in familial adenomatous polyposis. Gastrointest Gastrointest Endosc 2009;69:850–856. Endosc 2008;67:61–67. 76.Hartmann D, Eickhoff A, Damian U, et al. Diagnosis of 91.Tescher P, Macrae FA, Speer T, et al. Surveillance of small-bowel pathology using paired capsule endoscopy FAP: a prospective blinded comparison of capsule with two different devices: a randomized study. endoscopy and other GI imaging to detect small bowel Endoscopy 2007;39:1041–1045. polyps. Hered Cancer Clin Pract 2010;8:3. 77.Pioche M, Gaudin JL, Filoche B, et al. Prospective, ran- 92.Gupta A, Postgate AJ, Burling D, et al. A prospective domized comparison of two small-bowel capsule study of MR enterography versus capsule endoscopy for endoscopy systems in patients with obscure GI bleeding. the surveillance of adult patients with Peutz-Jeghers Gastrointest Endosc 2011;73:1181–1188. syndrome. AJR Am J Roentgenol 2010;195:108–116. 78.Min YW, Kim JS, Jeon SW, et al. Long-term outcome of 93.Mata A, Llach J, Castells A, et al. A prospective trial capsule endoscopy in obscure gastrointestinal bleeding: comparing wireless capsule endoscopy and barium a nationwide analysis. Endoscopy 2014;46:59–65. contrast series for small-bowel surveillance in hereditary 79.Koulaouzidis A, Rondonotti E, Giannakou A, et al. Diag- GI polyposis syndromes. Gastrointest Endosc 2005; nostic yield of small-bowel capsule endoscopy in pa- 61:721–725. tients with iron-deficiency anemia: a systematic review. 94.Ohmiya N, Nakamura M, Takenaka H, et al. Management Gastrointest Endosc 2012;76:983–992. of small-bowel polyps in Peutz-Jeghers syndrome by 512 Enns et al Gastroenterology Vol. 152, No. 3

using enteroclysis, double-balloon enteroscopy, and colonoscopy: a prospective, comparative trial. Gut 2015; videocapsule endoscopy. Gastrointest Endosc 2010; 64:272–281. 72:1209–1216. 109.Hassan C, Zullo A, Winn S, et al. Cost-effectiveness of 95.Rokkas T, Papaxoinis K, Triantafyllou K, et al. A meta- capsule endoscopy in screening for colorectal cancer. analysis evaluating the accuracy of colon capsule Endoscopy 2008;40:414–421. endoscopy in detecting colon polyps. Gastrointest 110.Gawron AJ, Veerappan A, Keswani RN. High success Endosc 2010;71:792–798. rate of repeat colonoscopy with standard endoscopes in 96.Spada C, Hassan C, Marmo R, et al. Meta-analysis patients referred for prior incomplete colonoscopy. BMC shows colon capsule endoscopy is effective in detecting Gastroenterol 2014;14:56. colorectal polyps. Clin Gastroenterol Hepatol 2010; 111.Brahmania M, Park J, Svarta S, et al. Incomplete colo- 8:516–522. noscopy: maximizing completion rates of gastroenterol- 97.Eliakim R, Yassin K, Niv Y, et al. Prospective multicenter ogists. Can J Gastroenterol 2012;26:589–592. performance evaluation of the second-generation colon 112.Food and Drug Administration. PillCam® COLON 2 capsule compared with colonoscopy. Endoscopy 2009; capsule endoscopy system last update 2014. Available 41:1026–1031. at: http://www.accessdata.fda.gov/cdrh_docs/pdf12/ 98.Spada C, Hassan C, Munoz-Navas M, et al. Second- K123666.pdf. Accessed: August 22, 2016. generation colon capsule endoscopy compared with 113.Given imaging receives reimbursement approval for Pill- colonoscopy. Gastrointest Endosc 2011;74:581–589 e1. Cam COLON® in Japan effective January 1, 2014. Globe- 99.Gay G, Delvaux M, Frederic M, et al. Could the colonic Newswire. Last update 2013. Available at: http://www. capsule PillCam Colon be clinically useful for selecting globenewswire.com/news-release/2013/11/11/588474/ patients who deserve a complete colonoscopy?: results 10057254/en/Photo-Release-Given-Imaging-Receives- of clinical comparison with colonoscopy in the Reimbursement-Approval-for-PillCam:R-in-Japan-Effective- perspective of colorectal cancer screening. Am J January-1-2014.html. Accessed: August 22, 2016. Gastroenterol 2010;105:1076–1086. 114.Meister T, Heinzow HS, Domagk D, et al. Colon capsule 100.Hagel AF, Gabele E, Raithel M, et al. Colon capsule endoscopy versus standard colonoscopy in assessing endoscopy: detection of colonic polyps compared with disease activity of ulcerative colitis: a prospective trial. conventional colonoscopy and visualization of extrac- Tech Coloproctol 2013;17:641–646. olonic pathologies. Can J Gastroenterol Hepatol 2014; 115.Sung J, Ho KY, Chiu HM, et al. The use of Pillcam Colon 28:77–82. in assessing mucosal inflammation in ulcerative colitis: a 101.Pilz JB, Portmann S, Peter S, et al. Colon capsule multicenter study. Endoscopy 2012;44:754–758. endoscopy compared to conventional colonoscopy un- 116.D’Haens G, Lowenberg M, Samaan MA, et al. Safety and der routine screening conditions. BMC Gastroenterol feasibility of using the second-generation pillcam colon 2010;10:66. capsule to assess active colonic Crohn’s disease. Clin 102.Rondonotti E, Borghi C, Mandelli G, et al. Accuracy of Gastroenterol Hepatol 2015;13:1480–1486 e3. capsule colonoscopy and computed tomographic colo- 117.Greenfield S, Kaplan S, Ware JE Jr. Expanding patient nography in individuals with positive results from the involvement in care. Effects on patient outcomes. Ann test. Clin Gastroenterol Hepatol 2014; Intern Med 1985;102:520–528. 12:1303–1310. 118.Stewart MA. Effective physician-patient com- 103.Alarcon-Fernandez O, Ramos L, Adrian-de-Ganzo Z, munication and health outcomes: a review. CMAJ 1995; et al. Effects of colon capsule endoscopy on medical 152:1423–1433. decision making in patients with incomplete colo- 119.Davis RE, Jacklin R, Sevdalis N, et al. Patient involve- noscopies. Clin Gastroenterol Hepatol 2013;11: ment in patient safety: what factors influence patient 534–540 e1. participation and engagement? Health Expect 2007; 104.Pioche M, de Leusse A, Filoche B, et al. Prospective 10:259–267. multicenter evaluation of colon capsule examination 120.Hoog CM, Bark LA, Arkani J, et al. Capsule retentions indicated by colonoscopy failure or anesthesia and incomplete capsule endoscopy examinations: an contraindication. Endoscopy 2012;44:911–916. analysis of 2300 examinations. Gastroenterol Res Pract 105.Triantafyllou K, Viazis N, Tsibouris P, et al. Colon capsule 2012;2012:518718. endoscopy is feasible to perform after incomplete colo- 121.Liao Z, Gao R, Xu C, et al. Indications and detection, noscopy and guides further workup in clinical practice. completion, and retention rates of small-bowel capsule Gastrointest Endosc 2014;79:307–316. endoscopy: a systematic review. Gastrointest Endosc 106.Negreanu L, Babiuc R, Bengus A, et al. PillCam Colon 2 2010;71:280–286. capsule in patients unable or unwilling to undergo colo- 122.Hara AK, Leighton JA, Heigh RI, et al. Crohn disease noscopy. World J Gastrointest Endosc 2013;5:559–567. of the small bowel: preliminary comparison among 107.Rex DK, Lieberman DA. A survey of potential adherence CT enterography, capsule endoscopy, small-bowel to capsule colonoscopy in patients who have accepted follow-through, and ileoscopy. Radiology 2006; or declined conventional colonoscopy. J Clin 238:128–134. Gastroenterol 2012;46:691–695. 123.Ou G, Shahidi N, Galorport C, et al. Effect of longer 108.Spada C, Hassan C, Barbaro B, et al. Colon capsule battery life on small bowel capsule endoscopy. World J versus CT colonography in patients with incomplete Gastroenterol 2015;21:2677–2682. February 2017 Consensus Guidelines for the Use of CE 513

124.Dolak W, Kulnigg-Dabsch S, Evstatiev R, et al. 140.Yazici C, Losurdo J, Brown MD, et al. Inpatient A randomized head-to-head study of small-bowel capsule endoscopy leads to frequent incomplete small imaging comparing MiroCam and EndoCapsule. bowel examinations. World J Gastroenterol 2012; Endoscopy 2012;44:1012–1020. 18:5051–5057. 125.Atay O, Mahajan L, Kay M, et al. Risk of capsule endo- 141.Hoog CM, Lindberg G, Sjoqvist U. Findings in patients scope retention in pediatric patients: a large single- with chronic intestinal dysmotility investigated by center experience and review of the literature. J Pediatr capsule endoscopy. BMC Gastroenterol 2007;7:29. Gastroenterol Nutr 2009;49:196–201. 142.Shiotani A, Honda K, Kawakami M, et al. Use of an 126.Cheifetz AS, Kornbluth AA, Legnani P, et al. The risk of external real-time image viewer coupled with pre- retention of the capsule endoscope in patients with specified actions enhanced the complete examinations known or suspected Crohn’s disease. Am J for capsule endoscopy. J Gastroenterol Hepatol 2011; Gastroenterol 2006;101:2218–2222. 26:1270–1274. 127.Baichi MM, Arifuddin RM, Mantry PS. Small-bowel 143.Cuschieri JR, Osman MN, Wong RC, et al. Small bowel masses found and missed on capsule endoscopy capsule endoscopy in patients with cardiac pacemakers for obscure bleeding. Scand J Gastroenterol 2007; and implantable cardioverter defibrillators: outcome 42:1127–1132. analysis using telemetry review. World J Gastrointest 128.Singeap AM, Trifan A, Cojocariu C, et al. Outcomes after Endosc 2012;4:87–93. symptomatic capsule retention in suspected small bowel 144.Harris LA, Hansel SL, Rajan E, et al. Capsule endoscopy obstruction. Eur J Gastroenterol Hepatol 2011;23:886–890. in patients with implantable electromedical devices is 129.Al-Bawardy B, Locke G, Huprich JE, et al. Retained safe. Gastroenterol Res Pract 2013;2013:959234. capsule endoscopy in a large tertiary care academic 145.Bandorski D, Irnich W, Bruck M, et al. Capsule endos- practice and radiologic predictors of retention. Inflamm copy and cardiac pacemakers: investigation for possible Bowel Dis 2015;21:2158–2164. interference. Endoscopy 2008;40:36–39. 130.Rogers AM, Kuperman E, Puleo FJ, et al. Intestinal 146.Bandorski D, Jakobs R, Bruck M, et al. Capsule endos- obstruction by capsule endoscopy in a patient with copy in patients with cardiac pacemakers and implant- radiation enteritis. JSLS 2008;12:85–87. able cardioverter defibrillators: (re)evaluation of the 131.Chong AK, Chin BW, Meredith CG. Clinically significant current state in Germany, Austria, and Switzerland 2010. small-bowel pathology identified by double-balloon Gastroenterol Res Pract 2012;2012:717408. enteroscopy but missed by capsule endoscopy. 147.Kotwal VS, Attar BM, Gupta S, et al. Should bowel Gastrointest Endosc 2006;64:445–449. preparation, antifoaming agents, or prokinetics be used 132.Banerjee R, Bhargav P, Reddy P, et al. Safety and effi- before video capsule endoscopy? A systematic review cacy of the M2A patency capsule for diagnosis of critical and meta-analysis. Eur J Gastroenterol Hepatol 2014; intestinal patency: results of a prospective clinical trial. 26:137–145. J Gastroenterol Hepatol 2007;22:2060–2063. 148.Belsey J, Crosta C, Epstein O, et al. Meta-analysis: 133.Boivin ML, Lochs H, Voderholzer WA. Does passage of a efficacy of small bowel preparation for small bowel patency capsule indicate small-bowel patency? A pro- video capsule endoscopy. Curr Med Res Opin 2012; spective clinical trial? Endoscopy 2005;37:808–815. 28:1883–1890. 134.Herrerias JM, Leighton JA, Costamagna G, et al. 149.Koulaouzidis A, Giannakou A, Yung DE, et al. Do proki- Agile patency system eliminates risk of capsule retention netics influence the completion rate in small-bowel in patients with known intestinal strictures who capsule endoscopy? A systematic review and meta- undergo capsule endoscopy. Gastrointest Endosc 2008; analysis. Curr Med Res Opin 2013;29:1171–1185. 67:902–909. 150.Rokkas T, Papaxoinis K, Triantafyllou K, et al. Does 135.Postgate AJ, Burling D, Gupta A, et al. Safety, reliability purgative preparation influence the diagnostic yield of and limitations of the given patency capsule in patients at small bowel video capsule endoscopy?: a meta-analysis. risk of capsule retention: a 3-year technical review. Dig Am J Gastroenterol 2009;104:219–227. Dis Sci 2008;53:2732–2738. 151.Wu L, Cao Y, Liao C, et al. Systematic review and 136.Yadav A, Heigh RI, Hara AK, et al. Performance of the meta-analysis of randomized controlled trials of sime- patency capsule compared with nonenteroclysis radiologic thicone for gastrointestinal endoscopic visibility. Scand examinations in patients with known or suspected intestinal J Gastroenterol 2011;46:227–235. strictures. Gastrointest Endosc 2011;74:834–839. 152.Rosa BJ, Barbosa M, Magalhaes J, et al. Oral purgative 137.Nemeth A, Kopylov U, Koulaouzidis A, et al. Patency and simethicone before small bowel capsule endoscopy. capsule in patients with established Crohn’s disease World J Gastrointest Endosc 2013;5:67–73. undergoing videocapsule endoscopy of the small bowel 153.Oliva S, Cucchiara S, Spada C, et al. Small bowel (abstr P177). J Crohns Colitis 2015;9:S165. cleansing for capsule endoscopy in paediatric patients: a 138.Rozov-Ung I, Mreyoud A, Moore J, et al. Detection of prospective randomized single-blind study. Dig Liver Dis drug effects on gastric emptying and contractility using a 2014;46:51–55. wireless motility capsule. BMC Gastroenterol 2014;14:2. 154.Franke A, Hummel F, Knebel P, et al. Prospective eval- 139.Lee MM, Jacques A, Lam E, et al. Factors associated uation of small bowel preparation with bisacodyl and with incomplete small bowel capsule endoscopy studies. sodium phosphate for capsule endoscopy. World J World J Gastroenterol 2010;16:5329–5333. Gastroenterol 2008;14:2061–2064. 514 Enns et al Gastroenterology Vol. 152, No. 3

155.Kantianis A, Karagiannis S, Liatsos C, et al. Comparison 169.Jowell PS, Baillie J, Branch MS, et al. Quantitative assess- of two schemes of small bowel preparation for capsule ment of procedural competence. A prospective study of endoscopy with polyethylene glycol: a prospective, ran- training in endoscopic retrograde cholangiopancreatog- domized single-blind study. Eur J Gastroenterol Hepatol raphy. Ann Intern Med 1996;125:983–989. 2009;21:1140–1144. 170.Watkins JL, Etzkorn KP, Wiley TE, et al. Assessment of 156.Hosono K, Endo H, Sakai E, et al. Optimal approach for technical competence during ERCP training. Gastro- small bowel capsule endoscopy using polyethylene gly- intest Endosc 1996;44:411–415. col and metoclopramide with the assistance of a 171.Rajan E, Iyer PG, Oxentenko AS, et al. Training in small- real-time viewer. Digestion 2011;84:119–125. bowel capsule endoscopy: assessing and defining 157.Ito T, Ohata K, Ono A, et al. Prospective controlled study competency. Gastrointest Endosc 2013;78:617–622. on the effects of polyethylene glycol in capsule 172.Postgate A, Haycock A, Thomas-Gibson S, et al. endoscopy. World J Gastroenterol 2012;18:1789–1792. Computer-aided learning in capsule endoscopy leads to 158.Belsey J, Epstein O, Heresbach D. Systematic review: improvement in lesion recognition ability. Gastrointest oral bowel preparation for colonoscopy. Aliment Endosc 2009;70:310–316. Pharmacol Ther 2007;25:373–384. 173.Faigel DO, Baron TH, Adler DG, et al. ASGE guideline: 159.Armstrong D, Barkun A, Bridges R, et al. Canadian As- guidelines for credentialing and granting privileges sociation of Gastroenterology consensus guidelines on for capsule endoscopy. Gastrointest Endosc 2005; safety and quality indicators in endoscopy. Can J 61:503–505. Gastroenterol 2012;26:17–31. 160.Gralnek IM, Defranchis R, Seidman E, et al. Development of a capsule endoscopy scoring index for small bowel Reprint requests fl Address requests for reprints to: Robert A. Enns, MD, FRCPC, University of mucosal in ammatory change. Aliment Pharmacol Ther ’ – British Columbia, Division of Gastroenterology, St. Paul s Hospital, 770-1190 2008;27:146 154. Hornby Street, Vancouver, British Columbia, Canada V6Z 2K5. e-mail: 161.Cotter J, Dias de Castro F, Magalhaes J, et al. Validation [email protected]; fax: (604) 689-2004. of the Lewis score for the evaluation of small-bowel Acknowledgments Crohn’s disease activity. Endoscopy 2015;47:330–335. The consensus group would like to thank Pauline Lavigne and Steven fi 162.Monteiro S, Boal Carvalho P, Dias de Castro F, et al. Portelance (unaf liated), who provided medical writing services on their behalf, supported by funds from the Canadian Association of Capsule endoscopy: diagnostic accuracy of Lewis score Gastroenterology. in patients with suspected Crohn’s disease. Inflamm The CAG would like to thank Allergan, Covidien, and Olympus for their – generous support of the guideline process. The consensus group would like Bowel Dis 2015;21:2241 2246. to thank the following people for their contributions: Paul Sinclair and Lesley 163.Gal E, Geller A, Fraser G, et al. Assessment and valida- Marshall (CAG representatives, administrative and technical support, and tion of the new capsule endoscopy Crohn’s disease logistics assistance), and Pauline Lavigne and Steven Portelance (unaffiliated, editorial assistance). activity index (CECDAI). Dig Dis Sci 2008;53:1933–1937. Robert A. Enns and Lawrence Hookey reviewed the literature and drafted the 164.Niv Y, Ilani S, Levi Z, et al. Validation of the Capsule statements; Grigorios I. Leontiadis and Frances Tse assessed the evidence ’ and provided GRADE evaluations; all members of the CAG Video Capsule Endoscopy Crohn s Disease Activity Index (CECDAI or Endoscopy Consensus Group voted on the recommendations; and Robert A. Niv score): a multicenter prospective study. Endoscopy Enns and Lawrence Hookey wrote the draft guidelines, which then were 2012;44:21–26. reviewed, revised, and approved by all members of the consensus group. 165.Delvaux M, Friedman S, Keuchel M, et al. Structured Conflicts of interest terminology for capsule endoscopy: results of retro- These authors disclose the following: Charles Bernstein has performed consulting for Mylan Pharmaceuticals, has served on the advisory board for spective testing and validation in 766 small-bowel AbbVie, Janssen, Pfizer, and Takeda, has received research or educational investigations. Endoscopy 2005;37:945–950. grants/clinical trial funding from AbbVie, Janssen, Shire, and Takeda, and has served on the speaker’s bureau for AbbVie and Shire; David Armstrong 166.Korman LY, Delvaux M, Gay G, et al. Capsule endoscopy has served on the advisory board for AbbVie, Allergan, Janssen, Pfizer, and structured terminology (CEST): proposal of a standard- Lupin, has received research or educational grants/clinical trial funding from AbbVie, and has served on the speaker’s bureau for AbbVie, Allergan, Mylan, ized and structured terminology for reporting capsule fi – Pendopharm, Pentax, P zer, Shire, and Takeda; Robert A. Enns has served endoscopy procedures. Endoscopy 2005;37:951 959. on the speaker’s bureau for AbbVie, Actavis, Boston Medical, Conmed, 167.Pezzoli A, Cannizzaro R, Pennazio M, et al. Interobserver Cook, Covidien, Ferring, Gilead, Janssen, Merck, Olympus, Pendopharm, fi Pentax, Roche, Shire, Takeda, and Vantage; and Lawrence Hookey has agreement in describing video capsule endoscopy nd- received research or educational grants/clinical trial funding from Given ings: a multicentre prospective study. Dig Liver Dis 2011; Imaging, and served on the speaker’s bureau for Ferring. The remaining 43:126–131. authors disclose no conflicts. 168.Girelli CM, Porta P, Colombo E, et al. Development of a Funding novel index to discriminate bulge from mass on small- This guideline was supported through unrestricted grants to the Canadian Association of Gastroenterology by Allergan Canada, Covidien Canada ULC, bowel capsule endoscopy. Gastrointest Endosc 2011; a Medtronic company, and Olympus Canada Inc. who had no involvement in 74:1067–1074; quiz 1115 e1–e5. any aspect of the guideline development.